The interactions of lipoproteins and artery wall cells are being studied in this Specialized Center of Research on Atherosclerosis. The grant supports the coordinated efforts of eight tenured faculty members, two assistant professors and a number of research associates from Biochemistry, Medicine and Pathology who are investigating the factors controlling the pathogenesis and the regression of atherosclerosis. The program includes investigation of the structure, molecular interactions, synthesis, secretion, degradation and molecular metabolism of lipoproteins. There is special emphasis on the apoproteins of the various lipoproteins and radioimmunoassay approaches are being developed for several of them. The interactions of various serum lipoprotein fractions and components with the artery wall and with the multifunctional medial mesenchymal (smooth muscle) cells are being studied both in vivo and in vitro, especially their effects on cell proliferation, cell lipid metabolism, lipid accumulation as well as cell degeneration and necrosis. Immunohistochemical approaches and ultrastructural observations, sometimes in combination, are being used in these studies. Atherosclerosis reversal studies in intact animals, are being carried out. These regression studies involve chemical, morphological (including ultrastructural) and metabolic observations. The effects of lipoproteins and artery wall components on coagulation and fibronolysis are included in the Center activities. Exploratory work is beginning on the lipoproteins and the cells of patients with severe atherosclerosis and ischemic myocardial disease who have no evidence for any of the lipoprotein, metabolic or artery wall abnormalities. It is hoped that these studies will help identify new factors which contribute to ischemic heart disease in these patients.